Sulfate conjugation is an important pathway in the biotransformation of many neurotransmitters, hormones, drugs and other xenobiotics, and is catalyzed by cytosolic sulfotransferase enzymes designated “SULT.” SULT enzymes are encoded by a gene superfamily, which, in mammals, is divided into two families, SULT1 or phenol SULTs and SULT2 or hydroxysteroid SULTs. The SULT1 and SULT2 families share at least 45% amino acid sequence identity, while members of subfamilies within each family share at least 60% amino acid sequence identity. SULT1 subfamilies include the phenol (1A), thyroid hormone (1B), hydroxyarylamine (1C), and estrogen (1E) subfamilies. SULT2 subfamilies include two hydroxysteroid SULTs, 2A1 and 2B1.
Sulfotransferases use 3′-phosphoadenosine 5′-phosphosulfate (PAPS) as a sulfate donor during sulfate conjugation reactions. PAPS is synthesized from ATP and inorganic sulfate by PAPS synthetase (PAPSS). Two PAPSS genes, PAPSS1 and PAPSS2, have been identified in humans. Xu et al., Biochem. Biophys. Res. Commun. (2000) 268(2):437–444. The PAPSS1 cDNA is approximately 2.7 kb in length and was mapped to human chromosome band 4q24 by fluorescence in situ hybridization (FISH) analysis. The PAPSS2 cDNA is approximately 4.2 kb in length and was mapped to 10q22–23 by FISH.